At the population level, Mexican-Americans have rates of gallbladder disease, primarily cholelithiasis, which are at least two- to three-fold higher than comparable Caucasians or Blacks. Among Mexican-Americans in South Texas, and likely elsewhere, no other disease, save diabetes, dominates the health status as does gallbladder disease. In spite of the high rates and health impact, relatively little is known about the epidemiology of gallbladder disease in this group and even less about its familial aggregation. It is clear that the traditional conceptions are inadequate. The ethnic distribution of the disease closely parallels the degree of genetic admixture with Amerindians and we demonstrate that the risk in first degree relatives is twice that of random individuals or spouses implicating genetic sources of population and familial aggregation. The purpose of this research is to establish the prevalence of both symptomatic and asymptomatic gallbladder disease through the use of ultrasonography and to elucidate the risk factors of disease; including diabetes, body mass, lipids, serum bile acids and urinary steroids. Additionally, we will assess the degree to which the observed aggregation is due to genetic admixture with Amerindians and the genetic and environmental sources of familial aggregation. The design consists of a random sample of 1000 individuals residing in Starr County, Texas, from which 100 cases and 100 disease free controls will be selected. All screened individuals and first degree relatives of cases will have a comprehensive physical examination which will include ultrasound evaluation of the gallbladder and various laboratory and genetic marker determinations. In addition, the cases and controls will have serum bile acid and urinary steroid compositions determined. In addition to linkage and verification of relatedness, the genetic markers will be used to determine individual affinities to ancestral populations and these related to the distribution of disease. Approximately three years following initial examination, the controls will be re-examined to detect the development of symptomatic or "silent" gallbladder disease. This will allow evaluation of the sources of change in disease status. In summary, the research proposed will document at the population and family level the degree and sources of aggregation of gallbladder disease, its concomitants and association with other disease, most notably diabetes and obesity, and whether these diseases represent separate manifestations of a common cause or whether they are etiologically independent.